乳腺癌化疗药物敏感性与基因靶点关系研究进展
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摘要
近年来随着各种新药尤其是内分泌治疗药物、靶向药物的面市,乳腺癌治疗取得了很大进步。许多晚期乳腺癌和三阴性乳腺癌治疗,仍以化疗为主。如何更有针对性的选择化疗药物,成为临床非常重要的课题。本文对胸苷酸合成酶(TYMS)、拓扑异构酶2A(TOP2A)、微管蛋白β3(TUBB3)和切除修复交叉互补基因(ERCC1)等一些热点靶标基因在乳腺癌的研究现状进行综述。
In recent years,with the introduction of various new drugs,especially endocrine therapy drugs and targeted drugs,the treatment of breast cancer has made great progress,but the main treatment for advanced breast cancer and triple-negative breast cancer was still chemotherapy. How to choose the drugs more specifically is becoming a very important clinical issue. This paper will review the research status of some hot target genes in breast cancer,such as thymidylate synthetase( TYMS),tubulin beta 3( TUBB3),topoisomerase 2-alpha( TOP2 A)and excision repair cross complementation 1( ERCC1).
In recent years,with the introduction of various new drugs,especially endocrine therapy drugs and targeted drugs,the treatment of breast cancer has made great progress,but the main treatment for advanced breast cancer and triple-negative breast cancer was still chemotherapy. How to choose the drugs more specifically is becoming a very important clinical issue. This paper will review the research status of some hot target genes in breast cancer,such as thymidylate synthetase( TYMS),tubulin beta 3( TUBB3),topoisomerase 2-alpha( TOP2 A)and excision repair cross complementation 1( ERCC1).
引文
[1] DESANTIS C E,MA J,GODING SAUER A,et al. Breast cancer statistics,2017,racial disparity in mortality by state[J]. CA Cancer J Clin,2017,67(6):439-448.
[2]陈万清,郑荣寿.中国女性乳腺癌发病死亡和生存状况[J].中国肿瘤临床,2015,42(13):668-674.
[3] BRAUNSTEIN L Z,TAGHIAN A G. Molecular phenotype,multigene assays,and the locoregional management of breast cancer[J].Semin Radiat Oncol,2016,26(1):9-16.
[4] JHAN J R,ANDRECHEK E R. Triple-negative breast cancer and the potential for targeted therapy[J]. Pharmacogenomics,2017,18(17):1595-1609.
[5]张凤岐,沈燕,王珊珊,等.外周血中TYMS和ERCC1基因多态性对胃肠道肿瘤患者化疗疗效的评估[J].肿瘤防治研究,2014,41(8):906-910.
[6]周志忠,黎喜梅,黄东联,等. TYMS基因在64例肝癌患者中的表达[J].中国热带医学,2014,14(10):1175-1177.
[7] WENG Y,ZHANG J,TANG X,et al. Thymidylate synthase polymorphisms and hematological cancer risk:a meta-analysis[J].Leuk Lymphoma,2012,53(7):1345-1351.
[8] EMILIA B B,RAQUEL C,ANGEL C,et al. Delimiting allelic imbalance of TYMS by allele-specific analysis[J]. Medicine,2015,94(27):1091.
[9] GUAN X X,LIU H L,JU J F,et al. Genetic variant rs16430 6 bp> 0 bp at the microRNA-binding site in TYMS and risk of sporadic breast cancer risk in non-hispanic white women aged≤55years[J]. Mol Carcinog,2015,54(4):281-290.
[10]张凤春,徐海燕,徐光如,等.胸苷酸合成酶基因多态性与不同种族乳腺癌FEC方案化疗不良反应相关性研究[J].上海交通大学学报(医学版),2014,34(6):850-854.
[11] LAM S W,GUCHELAAR H J,BOVEN E. The role of pharmacogenetics in capecitabine efficacy and toxicity[J]. Cancer Treat Rev,2016,50(11):9-22.
[12] NICOLSON M C,FENNELL D A,FERRY D,et al. Thymidylate synthase expression and outcome of patients receiving pemetrexed for advanced nonsquamous non-small-cell lung cancer in a prospective blinded assessment phase II clinical trial[J]. J Thorac Oncol,2013,8(7):930-939.
[13]朱烨.探讨药物相关性靶标在乳腺癌个体化新辅助化疗中的意义[D].长沙:中南大学湘雅医院,2013.
[14]汤小江,周瑜辉,张伟. TOP2A基因表达与乳腺癌HER2通路的相关性[J].西安交通大学学报(医学版),2015,36(4):519-522.
[15] ZHENG H,LI X,CHEN C,et al. Quantum dot-based immunofluorescent imaging and quantitative detection of TOP2A and prognostic value in triple-negative breast cancer[J]. Int J Nanomed,201621(11):5519-5529.
[16] GREGORY M,HEESTAN D A,MARIA S,et al. Topoisomerase expression and amplification in solid tumours:Analysis of 24,262 patients[J]. Eur J Cancer,2017,83(1):80-87.
[17] MORDENTE A,MEUCCI E,MARTORANA G E. Topoisomerases and anthracyclines:recent advances and perspectives in anticancer therapy and prevention of cardiotoxicity[J]. Curr Med Chem,2017,24(15):1607-1626.
[18] PRESS M F,SAUTER G,BUYSE M,et al. Alteration of topoisomeraseⅡ-alpha gene in human breast cancer:association with responsiveness to anthracycline-based chemotherapy[J]. J Clin Oncol,2011,29(7):859-867.
[19] KONECNY G E,PAULETTI G,UNTCH M,et al. Association between HER2,TOP2A,and response to anthracycline-based preoperative chemotherapy in high-risk primary breast cancer[J].Breast Cancer Res Treat,2010,120(2):481-489.
[20] NIELSEN K V,EJLERTSEN B,MLLER S,et al. The value of TOP2A gene copy number variation as a biomarker in breast cancer:Update of DBCG trial 89D[J]. Acta Oncol,2008,47(4):725-734.
[21] EJLERTSEN B. Adjuvant chemotherapy in early breast cancer[J].Dan Med J,2016,63(5):5222.
[22] CHEN T,SUN Y,JI P,et al. Topoisomerase IIαin chromosome instability and personalized cancer therapy[J]. Oncogene,2015,34(31):4019-4931.
[23] FORMICA V,DOLDO E,ANTONETTI F R. Biological and predictive role of ERCC1 polymorphisms in cancer[J/OL]. Crit Rev Oncol Hematol,2017,111:e133-e143. https://www. croh-online. com/article/S1040-8428(16)30262-1/fulltext.
[24] BOGUSH T A,POPOVA A S,DUDKO E A,et al. ERCC1 as a marker of ovarian cancer resistance to platinum drugs[J]. Antibiot Khimioter,2015,60(3-4):42-50.
[25] ORFANIDIS K,WSTER P,LUNDMARK K,et al. Evaluation of tubulinβ-3 as a novel senescence-associated gene in melanocytic malignant transformation[J]. Pigment Cell Melanoma Res,2017,30(2):243-254.
[26]谢玲,刘丽,陈劼,等. ERCC1在恶性肿瘤患者外周血和肿瘤组织中表达的相关性研究[J].临床肿瘤学杂志,2016,21(1):47-51.
[27]陈曦,吴晶晶,张妍,等.三阴性乳腺癌临床病理特征及与药物敏感度蛋白的相关性[J].肿瘤防治研究,2014,41(5):439-442.
[28]王珊珊.外周血中肿瘤化疗敏感基因TYMS和ERCC1对胃肠道肿瘤患者化疗效果的评估作用[D].郑州:郑州大学,2013.
[29]魏昕,杨举伦.乳腺癌组织中ERCC1、Ki67、PCNA表达与蒽环类化疗药物敏感性的关系[J].中国免疫学杂志,2015,31(2):169-172.
[30] EL BAIOMY M A,E L KASHEF W F. ERCC1 expression in metastatic triple negative breast cancer patients treated with platinumbased chemotherapy[J]. Asian Pac J Cancer Prev,2017,18(2):507-513.
[31] KONG X Q,HUANG Y X,LI J L,et al. Prognostic value of vascular endothelial growth factor receptor 1 and class IIIβ-tubulin in survival for non-metastatic rectal cancer[J]. World J Gastrointest Oncol,2018,10(10):351-359.
[32]项友群,胡孝渠,郭贵龙,等.乳腺癌β3-微管蛋白表达与紫杉类药物化疗耐药的相关研究[J]. 2014,12(5):719-720.
[33] WANG M,LI W,XING X,et al. BRCA1 and STMN1 as prognostic markers in NSCLCs who received cisplatin-based adjuvant chemotherapy[J]. Oncotarget,2017,8(46):80869-80877.
[34] OKUDA K,TATEMATSU T,YANO M,et al. The relationship between the expression of thymidylate synthase,dihydropyrimidine dehydrogenase, orotate phosphoribosyl transferase, excision repair cross-complementation group 1 and class IIIβ-tubulin,and the therapeutic effect of S-1 or carboplatin plus paclitaxel in nonsmall-cell lung cancer[J]. Mol Clin Oncol,2018,9(1):21-29.
[35] MEAGHER N S,SCHUSTER K,VOSS A,et al. Does the primary site really matter? Profiling mucinous ovarian cancers of uncertain primary origin(MO-CUP)to personalise treatment and inform the design of clinical trials[J]. Gynecol Oncol,2018,150(3):527-533.
[2]陈万清,郑荣寿.中国女性乳腺癌发病死亡和生存状况[J].中国肿瘤临床,2015,42(13):668-674.
[3] BRAUNSTEIN L Z,TAGHIAN A G. Molecular phenotype,multigene assays,and the locoregional management of breast cancer[J].Semin Radiat Oncol,2016,26(1):9-16.
[4] JHAN J R,ANDRECHEK E R. Triple-negative breast cancer and the potential for targeted therapy[J]. Pharmacogenomics,2017,18(17):1595-1609.
[5]张凤岐,沈燕,王珊珊,等.外周血中TYMS和ERCC1基因多态性对胃肠道肿瘤患者化疗疗效的评估[J].肿瘤防治研究,2014,41(8):906-910.
[6]周志忠,黎喜梅,黄东联,等. TYMS基因在64例肝癌患者中的表达[J].中国热带医学,2014,14(10):1175-1177.
[7] WENG Y,ZHANG J,TANG X,et al. Thymidylate synthase polymorphisms and hematological cancer risk:a meta-analysis[J].Leuk Lymphoma,2012,53(7):1345-1351.
[8] EMILIA B B,RAQUEL C,ANGEL C,et al. Delimiting allelic imbalance of TYMS by allele-specific analysis[J]. Medicine,2015,94(27):1091.
[9] GUAN X X,LIU H L,JU J F,et al. Genetic variant rs16430 6 bp> 0 bp at the microRNA-binding site in TYMS and risk of sporadic breast cancer risk in non-hispanic white women aged≤55years[J]. Mol Carcinog,2015,54(4):281-290.
[10]张凤春,徐海燕,徐光如,等.胸苷酸合成酶基因多态性与不同种族乳腺癌FEC方案化疗不良反应相关性研究[J].上海交通大学学报(医学版),2014,34(6):850-854.
[11] LAM S W,GUCHELAAR H J,BOVEN E. The role of pharmacogenetics in capecitabine efficacy and toxicity[J]. Cancer Treat Rev,2016,50(11):9-22.
[12] NICOLSON M C,FENNELL D A,FERRY D,et al. Thymidylate synthase expression and outcome of patients receiving pemetrexed for advanced nonsquamous non-small-cell lung cancer in a prospective blinded assessment phase II clinical trial[J]. J Thorac Oncol,2013,8(7):930-939.
[13]朱烨.探讨药物相关性靶标在乳腺癌个体化新辅助化疗中的意义[D].长沙:中南大学湘雅医院,2013.
[14]汤小江,周瑜辉,张伟. TOP2A基因表达与乳腺癌HER2通路的相关性[J].西安交通大学学报(医学版),2015,36(4):519-522.
[15] ZHENG H,LI X,CHEN C,et al. Quantum dot-based immunofluorescent imaging and quantitative detection of TOP2A and prognostic value in triple-negative breast cancer[J]. Int J Nanomed,201621(11):5519-5529.
[16] GREGORY M,HEESTAN D A,MARIA S,et al. Topoisomerase expression and amplification in solid tumours:Analysis of 24,262 patients[J]. Eur J Cancer,2017,83(1):80-87.
[17] MORDENTE A,MEUCCI E,MARTORANA G E. Topoisomerases and anthracyclines:recent advances and perspectives in anticancer therapy and prevention of cardiotoxicity[J]. Curr Med Chem,2017,24(15):1607-1626.
[18] PRESS M F,SAUTER G,BUYSE M,et al. Alteration of topoisomeraseⅡ-alpha gene in human breast cancer:association with responsiveness to anthracycline-based chemotherapy[J]. J Clin Oncol,2011,29(7):859-867.
[19] KONECNY G E,PAULETTI G,UNTCH M,et al. Association between HER2,TOP2A,and response to anthracycline-based preoperative chemotherapy in high-risk primary breast cancer[J].Breast Cancer Res Treat,2010,120(2):481-489.
[20] NIELSEN K V,EJLERTSEN B,MLLER S,et al. The value of TOP2A gene copy number variation as a biomarker in breast cancer:Update of DBCG trial 89D[J]. Acta Oncol,2008,47(4):725-734.
[21] EJLERTSEN B. Adjuvant chemotherapy in early breast cancer[J].Dan Med J,2016,63(5):5222.
[22] CHEN T,SUN Y,JI P,et al. Topoisomerase IIαin chromosome instability and personalized cancer therapy[J]. Oncogene,2015,34(31):4019-4931.
[23] FORMICA V,DOLDO E,ANTONETTI F R. Biological and predictive role of ERCC1 polymorphisms in cancer[J/OL]. Crit Rev Oncol Hematol,2017,111:e133-e143. https://www. croh-online. com/article/S1040-8428(16)30262-1/fulltext.
[24] BOGUSH T A,POPOVA A S,DUDKO E A,et al. ERCC1 as a marker of ovarian cancer resistance to platinum drugs[J]. Antibiot Khimioter,2015,60(3-4):42-50.
[25] ORFANIDIS K,WSTER P,LUNDMARK K,et al. Evaluation of tubulinβ-3 as a novel senescence-associated gene in melanocytic malignant transformation[J]. Pigment Cell Melanoma Res,2017,30(2):243-254.
[26]谢玲,刘丽,陈劼,等. ERCC1在恶性肿瘤患者外周血和肿瘤组织中表达的相关性研究[J].临床肿瘤学杂志,2016,21(1):47-51.
[27]陈曦,吴晶晶,张妍,等.三阴性乳腺癌临床病理特征及与药物敏感度蛋白的相关性[J].肿瘤防治研究,2014,41(5):439-442.
[28]王珊珊.外周血中肿瘤化疗敏感基因TYMS和ERCC1对胃肠道肿瘤患者化疗效果的评估作用[D].郑州:郑州大学,2013.
[29]魏昕,杨举伦.乳腺癌组织中ERCC1、Ki67、PCNA表达与蒽环类化疗药物敏感性的关系[J].中国免疫学杂志,2015,31(2):169-172.
[30] EL BAIOMY M A,E L KASHEF W F. ERCC1 expression in metastatic triple negative breast cancer patients treated with platinumbased chemotherapy[J]. Asian Pac J Cancer Prev,2017,18(2):507-513.
[31] KONG X Q,HUANG Y X,LI J L,et al. Prognostic value of vascular endothelial growth factor receptor 1 and class IIIβ-tubulin in survival for non-metastatic rectal cancer[J]. World J Gastrointest Oncol,2018,10(10):351-359.
[32]项友群,胡孝渠,郭贵龙,等.乳腺癌β3-微管蛋白表达与紫杉类药物化疗耐药的相关研究[J]. 2014,12(5):719-720.
[33] WANG M,LI W,XING X,et al. BRCA1 and STMN1 as prognostic markers in NSCLCs who received cisplatin-based adjuvant chemotherapy[J]. Oncotarget,2017,8(46):80869-80877.
[34] OKUDA K,TATEMATSU T,YANO M,et al. The relationship between the expression of thymidylate synthase,dihydropyrimidine dehydrogenase, orotate phosphoribosyl transferase, excision repair cross-complementation group 1 and class IIIβ-tubulin,and the therapeutic effect of S-1 or carboplatin plus paclitaxel in nonsmall-cell lung cancer[J]. Mol Clin Oncol,2018,9(1):21-29.
[35] MEAGHER N S,SCHUSTER K,VOSS A,et al. Does the primary site really matter? Profiling mucinous ovarian cancers of uncertain primary origin(MO-CUP)to personalise treatment and inform the design of clinical trials[J]. Gynecol Oncol,2018,150(3):527-533.